Details for Patent: 7,767,678

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Which drugs does patent 7,767,678 protect, and when does it expire?

Patent 7,767,678 protects BOSULIF and is included in two NDAs.

Protection for BOSULIF has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has twenty-five patent family members in twenty-five countries.

Summary for Patent: 7,767,678

Title:	Crystalline forms of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile and methods of preparing the same
Abstract:	This invention is directed to a crystalline 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile monohydrate having an x-ray diffraction pattern wherein 2θ angles (°) of significant peaks are at about: 9.19, 11.48, 14.32, 19.16, 19.45, 20.46, 21.29, 22.33, 23.96, 24.95, 25.29, 25.84, 26.55, 27.61, and 29.51, and a transition temperature of about 109° C. to about 115° C.
Inventor(s):	Marc Sadler Tesconi, Gregg Feigelson, Henry Strong, Hong Wen
Assignee:	Wyeth LLC
Application Number:	US11/478,216
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,767,678
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 7,767,678: Linifanib Form I Crystal Scope, Claim Analysis, and Patent Landscape

U.S. Patent No. 7,767,678 protects a specific monohydrate crystalline form of linifanib, also known as ABT-869, together with its X-ray diffraction signature, thermal behavior, conversion methods, and selected pharmaceutical compositions. The patent does not broadly claim linifanib as a chemical compound or its therapeutic use. Its commercial relevance is limited because linifanib has not received FDA approval and no approved product is listed in the FDA Orange Book.

What drug and crystal form does U.S. Patent 7,767,678 cover?

The claimed active ingredient is linifanib, a small-molecule kinase inhibitor with the chemical name:

4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile.

The patent focuses on Form I, an isolated crystalline monohydrate of linifanib. The claims define Form I primarily through:

• Powder X-ray diffraction peaks;
• A transition temperature of approximately 109°C to 115°C, centered at about 112°C;
• Conversion of anhydrous or other polymorphic forms into Form I using water;
• Pharmaceutical compositions containing more than 50% by weight of Form I.

The patent therefore belongs to the solid-state and formulation portion of the linifanib patent estate, rather than the foundational compound patent estate.

Item	Patent 7,767,678 scope
Active ingredient	Linifanib, ABT-869
Solid form	Form I crystalline monohydrate
Primary analytical marker	Powder X-ray diffraction pattern
Thermal marker	Approx. 109°C-115°C transition temperature
Process protection	Conversion to Form I using heated or ambient water
Formulation protection	Form I with carriers, detergent, acetic acid, polyol and cellulose
Therapeutic-use claim	None apparent in the supplied claims
Biologic or biosimilar relevance	None
FDA status	Linifanib is not FDA approved
Orange Book status	No approved linifanib product listing identified

What do claims 1 through 5 protect?

Claims 1 through 5 are product-by-characterization claims directed to the Form I monohydrate.

Claims 1 and 2: X-ray diffraction-defined Form I

Claim 1 requires an isolated crystalline monohydrate having at least one of 15 specified 2θ peaks:

9.19, 11.48, 14.32, 19.16, 19.45, 20.46, 21.29, 22.33, 23.96, 24.95, 25.29, 25.84, 26.55, 27.61 and 29.51 degrees.

Claim 2 is narrower. It requires the complete set of 24 listed peaks, including secondary peaks such as 9.98, 14.85, 15.64, 19.71, 22.58, 28.42, 30.32, 31.40 and 32.39 degrees.

The principal distinction is claim breadth:

• Claim 1 uses “at least one” peak. On its face, this creates substantial breadth, because a material may satisfy the diffraction limitation with only one listed peak, provided it is the specified linifanib monohydrate.
• Claim 2 requires the more complete diffraction pattern and is materially narrower.
• Claim 3 further requires that the pattern be substantially as shown in Figure 1 as Pattern A.

The enforceability of claim 1 would likely depend on how the court construes “isolated crystalline form,” “significant peaks,” “about,” and whether a single peak is sufficient to identify the claimed polymorph reliably. A single diffraction peak may have limited discriminatory value if other linifanib forms share that reflection.

Claims 4 and 5: Thermal transition limitation

Claim 4 independently defines the monohydrate by a transition temperature to a liquid of approximately 109°C to 115°C. Claim 5 narrows the limitation to approximately 112°C.

These claims create an alternative route to infringement. A material could fall within claims 4 or 5 even if the accused party disputes the applicability or reproducibility of the X-ray pattern, assuming the claimed thermal transition can be established under the patent’s testing conditions.

Potential validity and infringement issues include:

• Whether “transition temperature to a liquid” is sufficiently definite;
• Whether the temperature is a melting point, desolvation event, or combined solid-state transition;
• The effect of heating rate, sample preparation, water content and instrument calibration;
• Whether the 109°C-115°C range distinguishes Form I from other hydrates or solvates.

How strong are the crystalline-form claims?

The strongest claims are likely claims 2, 3 and 5 because they contain more specific analytical limitations. Claim 1 is broader but potentially more vulnerable to indefiniteness, anticipation or non-infringement arguments.

Claim group	Protection	Relative breadth	Principal vulnerability
Claim 1	Form I monohydrate with at least one listed peak	Broad	“At least one” may not uniquely identify Form I
Claim 2	Full listed XRD peak set	Medium	Testing and peak-tolerance disputes
Claim 3	Pattern A substantially as shown in Figure 1	Narrow	Figure interpretation and reproducibility
Claim 4	Monohydrate with 109°C-115°C transition	Medium	Thermal event definition
Claim 5	Approximately 112°C transition	Narrow	Measurement variability and claim construction

A generic or follow-on manufacturer could avoid literal infringement by producing an anhydrous form, a different polymorph, a different hydrate or a salt, unless other patents in the linifanib estate cover those alternatives. The patent does not, based on the supplied claims, prevent all manufacture or use of linifanib.

What do claims 6 through 11 protect?

Claims 6 through 11 cover manufacturing methods for converting other linifanib solid forms into Form I monohydrate.

Heated-water conversion

Claim 6 covers treating anhydrous linifanib with heated water. Claim 8 narrows the water temperature to at least approximately 90°C, and claim 9 narrows it further to at least approximately 95°C.

The claim structure is:

1. Treat anhydrous linifanib with heated water.
2. Use water at least approximately 90°C.
3. Use water at least approximately 95°C.

These claims may reach a manufacturing crystallization, hydration or solid-form conversion step even if the final product is not sold under a brand name. The process must, however, satisfy the specific conversion requirements and produce the claimed Form I monohydrate.

Ambient-water conversion

Claim 7 covers conversion of specified linifanib polymorphs, identified as Patterns B, C, D and Form VI, by treatment with water. Claim 10 requires water at a temperature where no heat or cold source is applied. Claim 11 narrows this to room-temperature water.

This group is potentially important for process infringement because it covers conversion under relatively mild conditions. It may reach a wet-processing or slurry-aging step used during commercial-scale manufacture.

Claim	Process requirement
6	Treat anhydrous linifanib with heated water
7	Convert specified polymorphs to Form I using water
8	Heated water at least approximately 90°C
9	Heated water at least approximately 95°C
10	Water without applied heating or cooling
11	Room-temperature water

Process-claim limitations

The process claims do not appear to cover every method of producing Form I. They are limited by:

• The starting solid form;
• The use of water;
• Temperature conditions;
• Conversion to Form I.

A process using an organic solvent, solvent mixture, vapor hydration, controlled humidity or direct crystallization from solution may fall outside these claims unless it also satisfies the required water-treatment steps.

The claims may also create proof problems. A finished batch may show Form I without revealing whether the manufacturer used the patented conversion process. Process discovery, batch records, crystallization protocols and source-code or manufacturing-data analysis would be important in litigation.

What do claims 12 through 21 protect?

Claims 12 through 21 cover pharmaceutical compositions containing Form I.

Claim 12 requires:

• A therapeutically effective amount of crystalline linifanib;
• A pharmaceutically acceptable carrier;
• More than 50% by weight of that therapeutically effective amount consisting of the Form I X-ray pattern.

This is a composition claim, not a method-of-treatment claim. It does not expressly require a particular disease, dose, route of administration or clinical indication.

Acetic acid and detergent limitations

Claims 13 through 16 add acetic acid and detergent:

• Claim 13: acetic acid;
• Claim 14: detergent;
• Claim 15: approximately 0.5%-5.0% detergent and 0.01%-0.1% acetic acid by weight;
• Claim 16: approximately 2.0% detergent and 0.06% acetic acid.

These limitations indicate that the patent addresses stabilization, dispersion, solubilization or formulation performance in addition to polymorph control.

Carrier limitations

Claims 17 through 21 narrow the carrier system:

• Sugar, polyol, cellulose or combinations;
• Polyol and cellulose;
• Mannitol, sorbitol or xylitol;
• Mannitol;
• Individual amounts of Form I, mannitol and cellulose of approximately 20%-50% by weight.

Claim 21 may require careful construction. If the three components are each present at 20%-50%, their combined amount can range from 60% to 150% before accounting for other ingredients. The likely reading is that each component falls within the stated range and that the composition may contain additional excipients, but the claim language creates a potential indefiniteness or written-description issue depending on the specification and prosecution history.

What formulations are protected by U.S. Patent 7,767,678?

The formulation claims are narrower than the crystal claims because they require both Form I and defined excipient combinations.

Formulation feature	Claims
Form I comprising more than 50% of linifanib amount	12
Acetic acid	13
Detergent	14
0.5%-5.0% detergent and 0.01%-0.1% acetic acid	15
2.0% detergent and 0.06% acetic acid	16
Sugar, polyol or cellulose carrier	17
Polyol plus cellulose	18
Mannitol, sorbitol or xylitol	19
Mannitol	20
Form I, mannitol and cellulose each at 20%-50%	21

An oral solid dosage form containing Form I, mannitol and cellulose could implicate claims 12 and 17-21 if the quantitative and structural limitations are met. A formulation containing linifanib in a different polymorph, amorphous form or salt would not necessarily infringe these claims.

The supplied claims do not expressly cover injectable, transdermal, ophthalmic or inhaled formulations unless they meet the same Form I and excipient limitations.

When does U.S. Patent 7,767,678 lose exclusivity?

U.S. Patent 7,767,678 issued on August 3, 2010. Its ordinary patent term is generally measured from the effective nonprovisional or international filing date, not from the grant date. Based on the patent’s filing chronology, the nominal expiration would be expected in the 2026-2027 period, subject to the official USPTO term calculation, patent-term adjustment, terminal disclaimers and any applicable corrections.

Milestone	Date or status
U.S. patent number	7,767,678
Grant date	August 3, 2010
Technology	Linifanib Form I monohydrate and formulations
Expected term window	Approximately 2026-2027
Patent-term adjustment	Must be taken from the USPTO patent record
FDA approval	None for linifanib
Orange Book-listed product	None identified
Regulatory exclusivity	None identified

Patent expiration does not create a practical generic-launch opportunity by itself. A generic applicant needs an FDA-approved reference product and a viable abbreviated new drug application pathway. Because linifanib has not been approved, the patent’s commercial blocking value is substantially lower than that of a listed Orange Book patent.

What is the Orange Book status of linifanib?

Linifanib is not listed as an FDA-approved active ingredient in the Orange Book. The FDA has not approved an NDA for linifanib, and no approved linifanib reference listed drug is available for an ANDA applicant to copy.

Consequences include:

• No Orange Book patent listing for U.S. Patent 7,767,678;
• No standard Paragraph IV certification pathway against an approved linifanib product;
• No automatic 30-month stay based on this patent;
• No Hatch-Waxman market exclusivity linked to linifanib;
• No conventional generic-launch schedule.

A future sponsor could seek approval through a new drug application or another applicable pathway, but that would not be a routine ANDA launch against an existing reference product.

Have companies filed Paragraph IV challenges or patent litigation?

No commercially significant Paragraph IV challenge is apparent for U.S. Patent 7,767,678 because there is no approved linifanib reference product against which an ANDA could be filed.

No major U.S. patent litigation involving this patent is identified in the supplied record. The absence of Paragraph IV litigation is consistent with the regulatory history: linifanib development did not result in an approved product.

Potential disputes would more likely arise from:

• A new clinical developer seeking to commercialize linifanib;
• A manufacturing dispute involving Form I;
• A patent-infringement action based on commercial production;
• An inter partes review or post-grant validity challenge;
• A licensing transaction involving the broader ABT-869 portfolio.

How does this patent compare with the broader linifanib patent estate?

U.S. Patent 7,767,678 is a secondary patent relative to patents claiming the linifanib chemical structure, pharmaceutical compositions in broader terms, or therapeutic uses.

Patent category	Strategic role
Compound patent	Blocks linifanib itself and usually provides the broadest protection
Salt or solid-form patent	Protects a selected physical form, including Form I here
Formulation patent	Protects excipient combinations and dosage forms
Method-of-use patent	Protects treatment of specific diseases or patient populations
Manufacturing patent	Protects synthesis, purification or crystallization processes
Regulatory exclusivity	Provides market protection independent of patent claims

The supplied claims contain no explicit method-of-use claims. They also do not cover the entire chemical genus of kinase inhibitors. Their value depends on whether Form I is required for the final drug product or is merely one interchangeable solid form.

What geographic coverage does the patent provide?

U.S. Patent 7,767,678 provides rights only in the United States. Corresponding applications may exist in other jurisdictions through the related international and national patent family, but foreign rights must be assessed separately for:

• Patent grant status;
• Claim amendments;
• Expiration dates;
• Patent-term adjustments or extensions;
• Opposition or revocation proceedings;
• Local claim construction;
• National patentability standards.

A U.S. freedom-to-operate analysis cannot establish freedom to operate in Europe, Japan, China, Canada or other markets.

What generic and manufacturing risks exist?

The principal risk is not a conventional generic challenge. It is the possibility that a future linifanib developer or contract manufacturer uses Form I as the commercial solid form.

Risk levels by activity are:

Activity	Risk under Patent 7,767,678
Manufacturing Form I monohydrate	High if the product and process meet the claims
Selling a Form I-containing product	Potentially high under claims 1-5 and 12
Manufacturing anhydrous linifanib	Lower under the supplied claims
Manufacturing another polymorph	Lower, subject to conversion and final-product issues
Using heated water to convert anhydrous linifanib	High under claims 6, 8 and 9
Using room-temperature water to convert specified polymorphs	High under claims 7, 10 and 11
Selling a formulation with mannitol and cellulose	Claim-dependent
Developing a different salt or amorphous form	Potentially outside this patent

The broader patent estate remains decisive. Avoiding U.S. Patent 7,767,678 would not establish freedom to operate if a separate compound, use, formulation or process patent remains enforceable.

Key Takeaways

• U.S. Patent 7,767,678 is a solid-state patent covering linifanib Form I crystalline monohydrate.
• Claims 1-5 define the crystal through X-ray diffraction and thermal-transition characteristics.
• Claims 6-11 cover conversion of anhydrous or other polymorphic forms into Form I using water.
• Claims 12-21 cover selected Form I pharmaceutical compositions with acetic acid, detergent, mannitol, cellulose and related carriers.
• Claim 1 is broader but may face disputes over whether one X-ray peak adequately identifies the claimed form.
• Claims 2, 3 and 5 are narrower and analytically more specific.
• The patent issued August 3, 2010, with nominal expiration expected in approximately 2026-2027, subject to the official USPTO term calculation.
• Linifanib has not received FDA approval, and no Orange Book-listed linifanib product or standard Paragraph IV challenge is identified.
• The patent does not claim linifanib generally, a disease-treatment method or every formulation of the compound.
• Commercial risk depends on whether Form I is used as the drug product and whether separate compound, use or manufacturing patents remain in force.

FAQs

Is U.S. Patent 7,767,678 a patent on linifanib itself?

No. The supplied claims cover a particular crystalline monohydrate form, processes for producing it and selected compositions containing it. They do not broadly claim the linifanib molecule in every form.

Can a company avoid this patent by selling amorphous linifanib?

Potentially, but only if the amorphous product does not convert into or contain the claimed Form I and does not infringe other linifanib patents. The broader patent estate must be reviewed separately.

Does the patent cover a linifanib tablet with mannitol?

It can, if the tablet contains the claimed Form I pattern and satisfies the carrier and quantitative limitations in claims 12 and 17-21. The exact formulation composition and solid-state characterization would control.

Is a Paragraph IV certification required for a future linifanib product?

Not against this patent under the ordinary Hatch-Waxman framework unless an approved linifanib reference product and applicable ANDA pathway exist. Linifanib has no identified FDA-approved reference listed drug.

Does patent expiration eliminate all U.S. linifanib launch barriers?

No. Expiration of this crystal-form patent would remove only its enforceable restrictions. Separate compound, use, formulation, manufacturing, regulatory or contractual barriers could remain.

References

1. U.S. Patent No. 7,767,678. (2010). Crystalline forms of linifanib. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA Orange Book.

3. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs database. U.S. Department of Health and Human Services.

4. United States Patent and Trademark Office. (2024). Patent term calculator and patent term adjustment resources. U.S. Department of Commerce.

5. National Center for Biotechnology Information. (2024). PubChem compound summary for linifanib. National Library of Medicine.

Drugs Protected by US Patent 7,767,678

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pf Prism Cv	BOSULIF	bosutinib monohydrate	CAPSULE;ORAL	217729-001	Sep 26, 2023		RX	Yes	No	7,767,678*PED				Y
Pf Prism Cv	BOSULIF	bosutinib monohydrate	CAPSULE;ORAL	217729-002	Sep 26, 2023		RX	Yes	Yes	7,767,678*PED				Y
Pf Prism Cv	BOSULIF	bosutinib monohydrate	TABLET;ORAL	203341-001	Sep 4, 2012	AB	RX	Yes	Yes	7,767,678*PED				Y

International Family Members for US Patent 7,767,678

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1902029		C20140016 00110	Estonia
Argentina	054505
Australia	2006266045